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Self-amplifying RNA technology applied to the development of a universal influenza vaccine

Objective

Influenza (Flu) virus infections lead to thousands of deaths annually worldwide and billions of dollars of economic burden. Vaccination is the primary strategy for Flu prevention; however, effective protection requires a perfect match with the seasonal circulating strains. Seasonal vaccines target the hemagglutinin (HA) and neuraminidase (NA) proteins of the two predominant A and one B circulating strains, and induce high neutralizing antibody titers. Emerging Flu viruses escape host immunity by modifying HA glycosylation and masking the immunodominant epitopes of previous years’ strains. In consequence, yearly seasonal Flu vaccines have to be developed. Therefore, there is a need for a universal Flu vaccine that would protect against most variants.
Patterns of HA glycosylation show that there are only 5 – 6 alterations in a century of evolution, reflecting the limited possibilities for the virus to escape host immunity while retaining its infectivity. Therefore, by developing a vaccine that includes most relevant past seasonal (H1, H3, and B) and pandemic (H5, H7) strains, it might be feasible to develop a universal Flu vaccine.
The project will combine HA selection with the novel self-amplifying mRNA (SAM®) vaccine technology, which consists of a synthetic RNA delivered by lipid nanoparticles, and already proved immunogenic in mice with Flu H1 and H7. We will design five SAM(HA) vectors encoding combinations of four HA, prioritized to cover up to 20 relevant strains, and characterize their immunogenicity in mice by measuring hemagglutination-inhibition and virus neutralization titers. In-depth characterization of germinal center B cells and follicular helper T cells will be performed by mass cytometry (CyTOF). Finally, HA-specific CD4 and CD8 T-cell cytokine and cytotoxic responses will be determined by mass cytometry for correlates of protection.
At the end of this proposal, the development of a universal Flu vaccine should be achieved.

Field of science

  • /medical and health sciences/health sciences/infectious disease/RNA virus/influenza
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmaceutical drug/vaccines

Call for proposal

FP7-PEOPLE-2013-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

GLAXOSMITHKLINE VACCINES SRL
Address
Via Fiorentina 1
53100 Siena
Italy
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 187 414,80
Administrative Contact
Francesco Siciliano (Dr.)